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Personalised Medicine in Carcinoma of Unknown Primary

Molecular profiling and assays for tissue analysis

We met with Karim Fizazi from the Department of Medicine, Institut Gustave Roussy, Villejuif, France to discuss how personalised medicine can improve the treatment of patients with carcinoma of unknown primary (CUP), molecular profiling and assays for tissue analysis, and how to demonstrate the effectiveness of molecular diagnostic tests.

ESMO: What is the current situation in treating patients with carcinoma of unknown primary site?

Karim Fizazi: Patients with carcinoma of unknown primary still have a bad prognosis with just approximately ten months of estimated survival. So, it is still a very terrible disease for these patients. It is a significant category of patients in oncology, probably around three per cent of the total patient population and after twenty years of research, there is still no true standard of care.

We treat these patients with chemotherapy, including regimens like cisplatin, gemcitabine, or carboplatin and paclitaxel, but the response rate is not that high, and the impact on overall survival has never been demonstrated. So, this is still a very important unmet need in oncology.

ESMO: What is the importance of personalised medicine in helping to make the improvements in patients with CUP?

Karim Fizazi: Patients with carcinoma of unknown primary are surely a perfect model for personalised medicine. As an oncologist, basically what you want to know is where the cancer comes from, and this is what imaging in this case is not able to tell us. But maybe it is more important, to determine what the true biology is in there, so you can give the right drug to the right patient. That is the paradigm of personalised medicine.

ESMO: How important are molecular profiling tests in patients with CUP?

Karim Fizazi: In the future we hope that tests will identify the likely primary tumour and its related biology, so you can give the right drug to the right patient. Indeed, there are already series of tests developed by several companies using either RT-PCR or micro-analysis that can be done on the CUP tissue, the metastatic tissue and they can identify adequately the likely primary of cancer in approximately 80 per cent of cases, which is quite high. Now what we don’t know is whether doing this can impact on patient management and outcome.

ESMO: How do you demonstrate the effectiveness of molecular diagnostic tests?

Karim Fizazi: To demonstrate their impact we need randomised trials, and these are ongoing. In these trials we randomise patients to receive either, standard chemotherapy or to undergo testing to try and find the primary and adapt therapy accordingly. So you can use targeted therapy, or a different chemotherapy regimen, or hormonal therapy depending on the origin of the likely primary tumour. The hypothesis is that in doing so, we’ll be able to postpone cancer progression and hopefully improve overall survival as well.

ESMO: How optimistic are you that in the future we will be able to improve the outlook for patients with this type of cancer?

Karim Fizazi: Well, if we are honest, we haven't made any true, significant progress in the management of patients with carcinoma of unknown primary in the last twenty years. At least based on the results from clinical trials. Probably immunohistochemistry has made some progress and the different treatments that we are using in various cancers have also helped patients with carcinoma of unknown primary. Now we have the opportunity to do specific trials for these patients, and to personalise therapy based on these tests, which speculate on a specific primary cancer and maybe specific biology. And we also have the weapons to target that. So, I have some hope that this generation of trials will be able to demonstrate that indeed, using these tests can postpone progression in these patients.